Detailed assessment of axial and peripheral entheses and joints in axial spondyloarthritis and psoriatic arthritis patients treated with ixekizumab (DAPHNE): design of a 2-year phase IV trial applying whole-body MRI, MRI-based synthetic CT, and CT

Ixekizumab, an interleukin 17A inhibitor, has demonstrated efficacy in improving clinical and patient-reported outcomes in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). However, objective data regarding its effects on peripheral inflammation in joints and entheses, inflammation of the posterolateral spinal segments, and structural progression in the spine are lacking. In this study, we aim to address the abovementioned gaps by conducting a longitudinal investigation of the effects of ixekizumab on peripheral and axial inflammation and structural damage in patients with axSpA and PsA. Through comprehensive assessment using advanced imaging techniques such as whole-body magnetic resonance (WB-MRI) and detailed MRI evaluation of the spine, including MRI-based synthetic computed tomography (synthetic CT), and low-dose CT, we seek to investigate the therapeutic effectiveness of ixekizumab across different disease domains. DAPHNE (EU-CT 2024-510746-14–00) is a 2-year open-label investigator-initiated multi-center study conducted in Denmark. Sixty-five patients with axSpA and PsA (≥25 with each diagnosis; ≥10 PsA patients with imaging-documented axial involvement), with a clinical indication for biological disease-modifying antirheumatic drug therapy, will be treated with ixekizumab, and followed by clinical, laboratory, WB-MRI, radiography, and low dose CT of sacroiliac joints (SIJs) and spine. MRI will include T1-weighted and short tau inversion recovery (STIR) sequences and a sequence allowing the generation of CT-like “synthetic CT” MR images. Images will be evaluated by readers blinded for diagnosis and clinical and other imaging findings. Furthermore, new lesion definitions and evaluation methods for synthetic CT and low-dose CT will be sought developed and explored. Currently, there are no data on the objective assessment of enthesitis, inflammation of the posterolateral segments of the spine, or structural progression in the spine using modern imaging during ixekizumab treatment neither in PsA nor axSpA. Thus, a longitudinal study hereof - the DAPHNE study - is anticipated to significantly improve our understanding of the diverse disease manifestations in axSpA and PsA, and how they respond to ixekizumab treatment. Additionally, the study will provide valuable insights into new and improved imaging examination and evaluation methods. EU-CT 2024-510746-14-00.